NMR Nuclear Magnetic Resonance

Proton NMR

Index

NMR-basics

Anisotropy of Aromatic compounds: in plane and above

H H CH3 H H H
H

dring 7.27-6.95 ppm dMe -0.51 ppm

H CH3 H H H

H
H H H H

dring 8.14-8.64 ppm dMe -4.25 ppm

H H H H

H H H H

dOUTSIDE 9.28 ppm dINSIDE -2.99 ppm

H H H

Anisotropy: Aromatic

Electronic effects
H2C O H3C

Deshielded
+ H2C O H3C

O H

H
O

COOEt

COOEt

7.10 ppm
H

6.28 ppm
H COOEt EtOOC H

6.83 ppm

O
O

6.10 ppm

5.93 ppm 7.07 ppm

6.38 ppm

7.71 ppm

6.28 ppm

Electronic effects: conjugation with carbonyl

O
7

3 5 6 4 2

O
1

Electronic effects: conjugation with carbonyl

O
1 2

deshielded

4 6 5

7.75 6.20

Electronic effects: conjugation with heteroatom

H O

H C

+ O

H
S

shielded
S

6.06 ppm
H H

5.81 ppm
O

5.48 ppm 6.22 ppm

H

H O

H 5.78 ppm

4.82 ppm H

Electronic effects: no conjugation with heteroatom

O
4 2 5 3 1

6.5

6.0

5.5

5.0

4.5

4.0

3.5

Electronic effects: conjugation with heteroatom

O
4 2 5 3 1

shielded
2.65 2.60 2.55

6.35

6.30

4.95

4.90

7.0

6.5

6.0

5.5

5.0

4.5

4.0

3.5

3.0

2.5

Electronic effects: conjugation with carbonyl

o
p

CH3

deshielded
7.5
deshielded

8.0

Electronic effects: conjugation with heteroatom

H3C O

Shielded
shielded

o
p

7.3

7.2

7.1

7.0

6.9

6.8

7.5

7.0

6.5

6.0

5.5

5.0

4.5

4.0

3.5

Electronic effects: conjugation with heteroatom

H3C NH

m p

o
shielded

Shielded

7.0

6.5

7.5

7.0

6.5

6.0

5.5

5.0

4.5

4.0

3.5

3.0

2.5

Aromatic: inductive effect and resonance effect

7.5

7.4
Cl

7.3

7.2

7.1

7.0

6.9

7.4
Br

7.3

7.2

7.1

7.6

7.5

7.4

7.3

7.2

7.1

Hydrogen bond

Protons on Heteroatoms OH, NH, SH

Exchangeable (with D2O) Hydrogen bonding On Nitrogen (14N), as the spin state of that nuclei is 1, there can be partial coupling that produce broaden lines. There can be also full coupling that would produce 3 lines of equal intensity (I=1 has 3 orientations in a magnetic field)

Protons on Heteroatoms
OH
Aliphatic d 0.5-4.0 ppm (depend on Concentration) Intramolecular hydrogen bonding deshield OH and render it less sensitive to concentration

Usually OH exchange rapidly (no coupling with neighbors In DMSO or Acetone, the exchange rate is slower => there is coupling with neighbors Phenols : d 7.5-4.0 ppm Intramolecular bond 12-10 ppm Carboxylic Acids: Exist as Dimers 13.2-10 ppm

H2O signal moves with temperature

H2O

OH in DMSO
CH3-CH2-OH OH CH2 qd

(CH3)2 -CH-OH OH CH

Protons on Heteroatoms
NH : 14N: I=1 => 2I+1 lines NH has different rate of exchange 14N can relax quickly. Depending on relaxation rate, heteronuclear coupling will be visible or produce broadened peaks. R-NH : Aliphatic amines => rapid exchange
Sharp singlets : no coupling to N: d~3-0.5 ppm

R-NH: Amides, Pyrroles, Indoles, Carbamates

NH broad CHa shows coupling the NH

NH

Amide

Protonated Amines

Formamide

H{14N}-NMR

H-CO-NH2 H-NMR

NH: Amide, Pyrrole Indole

d: 8.5-5.0 ppm

In Amides: Slow rotation can show different isomers

O H H N CH3 H N H O CH3

In Amine Salt: Moderate Rate of exchange => broad peaks ~ d 8.5-6.0 ppm CHa => show coupling to NH+ Sometimes broad [NHx+] consist of 3 broad hump due to 14N coupling
1J NH

~ 50 Hz

SH
Slow exchange SH couple to CHa When shaken with D2O, SH Disapear d ~ 1.6 1.2 ppm Aliphatic SH d ~ 3.6 2.8 ppm Aromatic SH

Chemical Shift and Coupling

An example: C10H12O2
O CH3 CH3

I = 10 + 1 12/2 = 5 O-CH2-CH3 Me-C= J=7 Hz J=7 Hz

J=8 Hz
2H 2H

H3C

O O O

2H
CH3

3H

3H

O
H3C CH3

Me-C=C

X 4 = 12

H3C

CH3

Scalar coupling: Coupling through bond

n=0 1 2 3 4 5 6 1 1 1 1 1 3 2 3 1 1 1

2nI + 1 lines
a doublet
H3C CH3

4 6 4 1 1 5 10 10 5 1 1 6 15 20 15 6 1

b septet

2.70

2.5

2.0

1.5

Scalar coupling: Coupling through bond

n=0 1 2 3 4 5 6 1 1 1 1 1 3 2 3 1 1 1

2nI + 1 lines
m p o o b a a
Br

4 6 4 1 1 5 10 10 5 1 1 6 15 20 15 6 1

p
7.50 7.40 7.30 7.20 7.10 7.00

2 x triplet b

3.40

3.30

3.20

3.10

3.00

7.5

7.0

6.5

6.0

5.5

5.0

4.5

4.0

3.5

3.0

Scalar coupling: Coupling through bond

n=0 1 2 3 4 5 6 1 1 1 1 1 3 2 3 1 1 1

2nI + 1 lines

4 6 4 1 1 5 10 10 5 1 1 6 15 20 15 6 1

a
b a
Br

2 x triplet 1 quintet

c
b

3.0

2.5

2.0

Scalar coupling: Coupling through bond 2nI + 1 lines

n=0 1 2 3 4 5 6 1 1 1 1 1 3 2 3 1 1 1

C7 H14 O2 I = 7 -14/2 + 1 = 1
mult triplet triplet sixtet quintet quartet triplet J (Hz) 7 7 7 7 7 7 COMMENT CH3->(CH2) CH3->(CH2) CH2 (CH3, CH2) CH2 (CH2, CH2) =C- CH2 (CH3) CH2 -O (CH2)

4 6 4 1 1 5 10 10 5 1 1 6 15 20 15 6 1

d (ppm) 0.9 1.1 1.35 1.55 2.3 4.1

Int 3H 3H 2H 2H 2H 2H

CH3
Triplet: Roof effect CH2 0.9 ppm 1.35

CH2
CH2

CH2 2.3 CH3 1.1 O

2 x triplet 3H 3H

2H

Quartet:

2H

Quintet: Sixtet:

2H 2H

4.0

3.5

3.0

2.5

2.0

1.5

1.0

Scalar coupling: Coupling through bond

n=0 1 2 3 4 5 6 1 1 1 1 1 3 2 3 1 1 1

2nI + 1 lines

4 6 4 1 1 5 10 10 5 1 1 6 15 20 15 6 1

H3C
1 2

3 4

CH3
6

Triplet:

O
Quartet:

2 x triplet 6 1

Quintet: 3 Sixtet:

4.0

3.5

3.0

2.5

2.0

1.5

1.0

Common first order spin system 2nI + 1 lines

Ha
C

Hb
C

Hb Hb
C

Ha
C

Hb
C

Hb

Hb Ha
C

Hb

Hb
C

Hb Hb
C

Hb
C

Ha
C

Ha
C

Hb
C

Hb

Hb

Common first order spin system 2nI + 1 lines

Jab = Jab Ha Hb
C C

Hc Hb Hb
C Jab Jab C

Ha
C

Hb
C

Hb

qd

Hb
C

Ha
C

Hb

Jab
td

Hb
C

Ha
C

Hb
C

Hc Hb
C

Ha
C

Hb
C

Hb

Geminal Coupling

Vicinal Coupling

3J

=> Perch

3J 3J

=> tool 1
=> Mestrec tool

Using Vicinal Coupling to establish isomer

Ha

Jab Jad

Jac

Long Range Coupling

Long Range coupling

H
4

H
5

4J

N H
7

= 1.07 Hz 5J H1-H4 = 1.21 Hz 5J H1-H5 = 0.95 Hz 5J H4-H7 = 0.67 Hz

H1-H3

4J

H-H

= 9 Hz
C C H

H
1

5J

H-H

= 3 Hz

H H

4J

H-H

= 1-2 Hz

4J

H-H
C

= 3 Hz
C C H

4J

H-H

= 1.1 Hz

5J
H

H-H

= 3 Hz

Spin System in Pople notation

Structural Unit -CH2-CH3 Spin system A3X2
2.5 2.0 1.5

Partial spectrum

-CH-CH3

A3X
3.0 2.5 2.0 1.5

CH2-CH2-CH3

A3M2X2
2.0 1.5 1.0

Each chemical shift is represented by a letter (far way letter for very large shift difference compare with the size of the coupling)

Second Order spectra: AB instead of AX

As the difference in shift become smallercompare with the size of the coupling the outer peaks become smaller in intensity

Dn / J
J

Dn J
3 4

5.0
1 2

4.0 3.0

nA and nB : center of gravity of doublet Chemical shift Dn = (1-4) * (2-3) SpinWorks => load AB

2.0

1.0

0.5

AB-Spectra

AMX

C6 H4 O5 N2 I = 6 - 4/2 + 2/2 +1 I= 6 Phenyl = 4 I NO2 = 1 I

A2X and A2B

SpinWorks => load A2B

AMX

AMX
Substituants : 2 OMe (~ 3.9 ppm) CHO (~ 9.8 ppm) J Meta Para J Ortho Meta J Ortho Para OMe
H

OMe
OMe
H H

7.58 ppm

CHO
H

6.83 ppm 7.2 ppm

CHO
H

7.58 ppm

OMe
H

6.83 ppm 7.2 ppm

meta bromo nitro benzene

Br H
B

H
A

H
C

N H
D

+ -

Calculated shifts dHA=8.44 dHB=7.82

dHC=7.31

dHD=8.19

HA HB HD HC

8.5

8.0

7.5

AFMX

C5 H4 N Br I = 5 4/2 1/2 +1/2 +1 I = 4 (aromatic ring)

d J

Assignment of 1H NMR of: cartilagineal

Me

CHO

H H
8 7 6

Cl
5

H
3 4 2 9

Cl
1

Me Cl
O

CHO-9 J = 2.0 Hz
3J 3J

H-1(s)

H-3 ddd 3J =15.5 3,4 4J 3,5 =1.0 4J =2.0 4,9

Jcis=10.5
H
8

H
7

dd
R
6

J =17 H trans

Hz

H-5 dd 3J 4,5 = 8.5 4J 3,5 = 1.0

3,4=15.5 4,5

=8.5

H-4 dd

Complicated proton spectra : CH3-CH2-S-PF2

Almost quintet

3J

PH

3J

HH

3J

HH

4J

FH

Identifying 31P couplings

{31P}

R C C
P

P
H P H

dd

NMR From Spectra to Structures An Experimental approach Second edition (2007) Springler-Verlag Terence N. Mitchellm Burkhard Costisella

Identifying 31P couplings: another example

Ph, 2H

CH3
1H 1H

CH2

NMR From Spectra to Structures An Experimental approach Second edition (2007) Springler-Verlag Terence N. Mitchellm Burkhard Costisella

P31 NMR

Identifying 31P couplings: another example

NMR From Spectra to Structures An Experimental approach Second edition (2007) Springler-Verlag Terence N. Mitchellm Burkhard Costisella

H-nmr P31 decoupled 1H CH2

To identify a compound: PF215NHSiH3

Use as many techniques as possible Proton nmr spectra is difficult to analyze with so many Js But with 19F, 15N and 31P spectra its easier (get heteronuclear J)

To identify a compound: PF215NHSiH3

Use as many techniques as possible Using decoupler : easier analysis

Another example H{X}

Changing the solvent

Changing solvent can be used to improve dispersion of chemical shifts

C6D6

CDCl3

Changing the solvent

Me CH2

Me

=CH2 C6D6

H2 C OH Me

CH2 CH-OH

=CH2 CDCl3 CH-OH

CH2 ABX

Decoupling
Me CH2

Me

=CH2 CDCl3

H2 C OH Me

CH2 ABX

CH-OH

CH2 AB

Spin-Spin Decoupling

dq

dq

dd

NMR From Spectra to Structures An Experimental approach Second edition (2007) Springler-Verlag Terence N. Mitchellm Burkhard Costisella

Homo decoupling
JPH

JHH

Decoupling H-1 glucose derivative

H-2

H-1

Several Decoupling

NOE
nOe

NOE: applying gB2 to the A of an AX spin system

bb ba X2 A1 aa A2 X1 ab bb

{A}

ba

X2 A1 aa

A2 X1

ab

X1 Dp = 2 X2 Dp = 2

X1 Dp = 2 X2 Dp = 2

Immediately after irradiation, there is NO change in the intensity of X Turning on the Decoupler do not change population of the X transition

NOE: relaxation with double quantum pathway W2 probability (positive NOE)

bb ba X2 A1 aa A2 X1 ab {A} ba X2 A1 aa bb A2 ab

X1 Dp = 2 X2 Dp = 2

X1
delay

bb

bb A2 X1

ba

X2 A1

ab

T1

ba

X2 A1

W2
aa

A2 X1

ab

aa

Dec. continue

X1 Dp = 3 After W2 relaxation, there is a net increase in the intensity of X (50%) X2 Dp = 3 Relaxation takes time to establish a new equilibrium: T1 process

NOE: Relaxation with zero quantum pathway W0 probability (negative NOE)

bb ba X2 A1 aa A2 X1 ab {A} ba X2 A1 aa bb A2

X1 Dp = 2 X2 Dp = 2

X1
delay

ab

bb

bb A2 X1

ba

X2 A1

W0
aa

ab

T1

ba

X2 A1

W0
aa

A2 X1

ab

Dec. continue

X1 Dp = 1 After W0 relaxation, there is a net decrease in the intensity of X (50%) negative NOE X2 Dp = 1 Relaxation takes time to establish a new equilibrium: T1 process

NOE: summary of relaxation pathways

ba
X2 A1

W0

bb W2 A2

X1 aa

ab

W1: probability of single quantum relaxation do not create nOe

A new population ditribution is generated by relaxation through dipole-dipole relaxation : double quantum and zero quantum pathway W2 and W0

If W2 is efficient (small molecule fast motion large frequency ) Level increase level increase also with decoupler continuing W2 pathway yield positive nOe If W0 is efficient (large molecule slow motion small freq. Diff.) Level increase level increase also with decoupler continuing
W0 pathway yield negative nOe

NOE difference: nOe-d NOE is a kinetic effect: need delay ~ T1 It take time to develop It takes time to decay d1
Dec on frq

Cl C H C

Me Me

AQ irr

d1
Dec off frq

AQ

irr

control nOe

difference

NOE
H3C H

{Me cis} => +19% {Me trans} => -2%

H3C

COOH

{Ha} => +45%

Choosing a structure by nOe

OH H
6 5 1 2 3 4

Ph

{OH}
CH3 H

OMe

{OMe}
OMe H
6 5 1 2 3 4

Ph

CH3

H6 H3

H5

OH

NMR From Spectra to Structures An Experimental approach Second edition (2007) Springler-Verlag Terence N. Mitchellm Burkhard Costisella

NOEd

Cl

O CH P O O

CH3 CH3

Cl

NOEd example

Organometallic compounds Proton - NMR

Increasing the 1 s orbital density increases the shielding
M=C MH4 MH3I MH3Br MH3Cl (MH3)2O MH3F 0.1 2.0 2.5 2.8 3.2 4.1 M = Si 3.2 3.4 4.2 4.6 4.6 4.8 M = Ge 3.1 3.5 4.5 5.1 5.3 5.7

Shift to low field when the metal is heavier (SnH4 - d = 3.9 ppm)

Proton NMR : Chemical shift

Further contribution to shielding / deshielding is the anisotropic magnetic susceptibility from neighboring groups (e.g. Alkenes, Aromatic rings -> deshielding in the plane of the bound) In transition metal complexes there are often low-lying excited electronic states. When magnetic field is applied, it has the effect of mixing these to some extent with the ground state. Therefore the paramagnetic term is important for those nuclei themselves => large high frequency shifts (low field). The protons bound to these will be shielded (d => 0 to -40 ppm) (these resonances are good diagnostic. ) For transition metal hydride this range should be extended to 70 ppm! If paramagnetic species are to be included, the range can go to 1000 ppm!!

Exchange : DNMR Dynamic NMR

NMR is a convenient way to study rate of reactions provided that the lifetime of participating species are comparable to NMR time scale (10-5 s)
H H H GeMe3 H H

At low temperature, hydrogens form an A2B2X spin system At higher temperature germanium hop from one C to the next

Index

NMR-basics

NMR-Symmetry